Liu Fu-Shing, Dong Jin-Tang, Chen Jung-Ta, Hsieh Yeun-Ting, Ho Esther Shih-Chu, Hung Man-Jung, Lu Chien-Hsing, Chiou Li-Ching
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan 40705, Republic of China.
Clin Cancer Res. 2003 Apr;9(4):1393-8.
KAI1 is a metastasis suppressor gene located on human chromosome 11p11.2. It is a member of the structurally distinct family of cell surface glycoprotein, transmembrane 4 protein superfamily. KAI1 was initially isolated as a gene that suppressed metastasis of rat prostate tumor cells. Decreased KAI1 expression has been observed recently in various human cancers, including pancreatic, lung, hepatic, colorectal, breast, ovarian, esophageal, and cervical cancers. Frequent down-regulation of the KAI1 protein was also observed in endometrial cancer cell lines. The aim of this study was to determine whether this gene is altered in human endometrial carcinoma. In addition, its prognostic significance in this tumor was also evaluated.
Tumor specimens from 18 cases with various degrees of endometrial hyperplasia, 97 primary endometrial carcinomas with various stages, and 28 metastatic lesions of this cancer were examined in this study. Using the method of immunohistochemistry, we characterized the KAI1 protein expression in the 143 endometrial tumors. Expression of KAI1 at RNA level was also examined in 35 of the 143 samples using a real-time quantitative PCR method. The data from immunohistochemical analysis were correlated with various clinicopathological factors.
High levels of KAI1 protein expression were detected in almost all of the specimens with endometrial hyperplasia (17 of 18). In contrast, loss of KAI1 expression occurred in an increasing frequency (27.8-71.4%) from early stages of primary endometrial carcinomas to metastatic tumors (P < 0.001). In addition, more poorly differentiated tumors demonstrated significantly lower KAI1 expression as compared with the well-differentiated tumors (P < 0.001). It was also found that patients with KAI1-negative tumors had a lower survival rate than those with KAI1-decreased or positive tumors (P = 0.0042 and 0.0286, respectively). However, in multivariate analysis, the prognostic significance of KAI1 expression was inferior to tumor stage.
These data suggest that KAI1 expression is down-regulated in advanced endometrial cancer. Clinically it may be a useful indicator of the tumor progression and may provide prognostic information on the outcome of this disease.
KAI1是一种位于人类染色体11p11.2上的转移抑制基因。它是结构独特的细胞表面糖蛋白跨膜4蛋白超家族的成员。KAI1最初是作为一种抑制大鼠前列腺肿瘤细胞转移的基因被分离出来的。最近在包括胰腺癌、肺癌、肝癌、结直肠癌、乳腺癌、卵巢癌、食管癌和宫颈癌在内的各种人类癌症中均观察到KAI1表达降低。在子宫内膜癌细胞系中也经常观察到KAI1蛋白的下调。本研究的目的是确定该基因在人类子宫内膜癌中是否发生改变。此外，还评估了其在该肿瘤中的预后意义。
本研究检测了18例不同程度子宫内膜增生、97例不同分期的原发性子宫内膜癌以及28例该癌症转移灶的肿瘤标本。采用免疫组化方法，我们对143例子宫内膜肿瘤中的KAI1蛋白表达进行了特征分析。还使用实时定量PCR方法检测了143例样本中的35例KAI1在RNA水平的表达。免疫组化分析的数据与各种临床病理因素相关。
几乎所有子宫内膜增生标本（18例中的17例）中均检测到高水平的KAI1蛋白表达。相比之下，从原发性子宫内膜癌早期到转移瘤，KAI1表达缺失的频率逐渐增加（27.8 - 71.4%）（P < 0.001）。此外，与高分化肿瘤相比，低分化肿瘤的KAI1表达明显更低（P < 0.001）。还发现KAI1阴性肿瘤患者的生存率低于KAI1表达降低或阳性肿瘤患者（分别为P = 0.0042和0.0286）。然而，在多变量分析中，KAI1表达的预后意义不如肿瘤分期。
这些数据表明KAI1表达在晚期子宫内膜癌中下调。临床上它可能是肿瘤进展的有用指标，并可能提供关于该疾病预后的信息。
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